[Beta-adrenolytics in heart failure--are they all really equal?]

The Carvedilol or Metoprolol European Trial (COMET) found that in patients with heart failure, survival appears to be better with carvedilol than with immediate-release metoprolol. Whether the target doses used were equivalent (carvedilol 25 mg twice daily; mean daily dose 85 mg vs metoprolol 50 mg twice daily; mean daily dose 42 mg) has been debated, but the COMET trial shows that drugs in the same class do not necessarily have the same effects. Given the overwhelming evidence of the benefit of carvedilol, metoprolol, and bisoprolol in patients with heart failure, we should all work to increase the use of these drugs in appropriate doses. Carvedilol and metoprolol both decrease mortality in heart failure, although their pharmacological profiles differ a lot. It is not clear whether the ancillary properties, which carvedilol has, but metoprolol does not assess, contribute to its beneficial effect. In COMET trial all-cause mortality was less in the carvedilol than the metoprolol group, indicating that at trial doses, carvedilol has a mortality benefit over metoprolol. However, the beta(1)-adrenoceptor blocking activity of metoprolol (assessed by a decrease in heart rate) was slightly less than with carvedilol in COMET and less than that observed in previous mortality studies with metoprolol, suggesting that the use of metoprolol was not optimal in COMET. Nevertheless, we may conclude all beta-adrenolytics used in heart failure are not really equal as far as evidence-based medicine data are currently concerned. The article summarizes some new investigations into ancillary properties of carvedilol which may decide of its special position among beta-adrenolytices used in heart failure.